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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2010-10-22
pubmed:abstractText
Stimulation of the TNF receptors CD30 and CD95 exerts opposite effects. Crosstalk of both receptors is unknown. We aimed to reveal regulatory mechanisms of CD30-induced effects on CD95 signaling of cALCL cell lines. "CD30/CD95 crosstalk analysis" was performed in cALCL cell lines by comparison of CD30 or CD95 stimulation and CD30/CD95 costimulation. Receptor expression and induction of apoptosis was investigated by flow cytometry. mRNA expression of CD30-inducible genes (cFLIP, TRAF1, cIAP2, and A20) was compared by semiquantitative reverse transcription (RT-RQ-) PCR in stimulated and unstimulated cells. Protein expression of I?B?, p100/p52, caspase-8, caspase-3, and cFLIP was analyzed by immunoblotting. A lentiviral-based shRNA-mediated approach was used to inhibit cFLIP expression. CD30/CD95 crosstalk experiments revealed that CD30 ligation leads to NF?B-mediated cFLIP upregulation in cALCL cells, which in turn enhanced resistance to CD95-mediated apoptosis. This effect is based on the CD30-induced upregulation of cFLIP. Knockdown of cFLIP restores sensitivity to CD95-mediated apoptosis. We conclude that the anti-apoptotic function of CD30 antibodies should be kept in mind if CD30 antibody-based therapeutic concepts for ALCL lymphoma are considered.
pubmed:language
ger
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1432-1963
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
31 Suppl 2
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
193-8
pubmed:meshHeading
pubmed-meshheading:20812013-Antigens, CD30, pubmed-meshheading:20812013-Antigens, CD95, pubmed-meshheading:20812013-Apoptosis, pubmed-meshheading:20812013-CASP8 and FADD-Like Apoptosis Regulating Protein, pubmed-meshheading:20812013-Cell Line, Tumor, pubmed-meshheading:20812013-Flow Cytometry, pubmed-meshheading:20812013-Gene Expression Regulation, Neoplastic, pubmed-meshheading:20812013-Humans, pubmed-meshheading:20812013-Lymphoma, Large-Cell, Anaplastic, pubmed-meshheading:20812013-Lymphoma, T-Cell, Cutaneous, pubmed-meshheading:20812013-RNA, Messenger, pubmed-meshheading:20812013-Receptor Cross-Talk, pubmed-meshheading:20812013-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:20812013-Skin, pubmed-meshheading:20812013-Skin Neoplasms, pubmed-meshheading:20812013-Up-Regulation
pubmed:year
2010
pubmed:articleTitle
[cFLIP diminishes CD95-induced apoptosis of CD30-stimulated cutaneous anaplastic large T cell lymphoma (cALCL) cells].
pubmed:affiliation
Institut für Pathologie, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin. burkhard.hirsch@charite.de
pubmed:publicationType
Journal Article, English Abstract